Project description:Mitochondrial biogenesis requires precise regulation of both mitochondrial-encoded and nuclear-encoded genes. Nuclear receptor Nur77 is known to regulate mitochondrial metabolism in macrophages and skeletal muscle cells. Here, we compared genome-wide Nur77 binding site and target gene expression in these two cell types, which revealed conserved roles for this nuclear receptor in the regulation of nuclear-encoded mitochondrial ribosomal proteins (MRP) and enrichment of motifs for the transcription factor Yin-Yang 1 (YY1). We show that Nur77 and YY1 interact, that YY1 increases Nur77 activity, and that their binding sites are co-enriched at MRP gene loci. Nur77 and YY1 co-expression synergistically increases mitochondrial abundance and activity in macrophages but not skeletal muscle. As such, we identify a macrophage-specific Nur77-YY1 interaction that enhances mitochondrial metabolism.
Project description:Mitochondrial biogenesis requires precise regulation of both mitochondrial-encoded and nuclear-encoded genes. Nuclear receptor Nur77 is known to regulate mitochondrial metabolism in macrophages and skeletal muscle cells. Here, we compared genome-wide Nur77 binding site and target gene expression in these two cell types, which revealed conserved roles for this nuclear receptor in the regulation of nuclear-encoded mitochondrial ribosomal proteins (MRP) and enrichment of motifs for the transcription factor Yin-Yang 1 (YY1). We show that Nur77 and YY1 interact, that YY1 increases Nur77 activity, and that their binding sites are co-enriched at MRP gene loci. Nur77 and YY1 co-expression synergistically increases mitochondrial abundance and activity in macrophages but not skeletal muscle. As such, we identify a macrophage-specific Nur77-YY1 interaction that enhances mitochondrial metabolism.
Project description:Investigate genes expression profiles of postmenopausal osteoporosis with kidney Yin deficiency in peripheral blood By TCM syndrome, 10 patients with postmenopausal osteoporosis were divided into three groups: kidney Yin deficiency (n=4), kidney Yang deficiency (n=3), non-kidney deficiency (n=3), another 3 healthy postmenopausal women also were selected as control group. Whole human genome oligo microarray were applied to explore gene expression difference of the groups. Kidney Yin deficiency group was compared with other three groups respectively.
Project description:Diverse subpopulations of astrocytes tile different brain regions to accommodate local requirements of neurons and associated neuronal circuits. Nevertheless, molecular mechanisms governing astrocyte diversity remain mostly unknown. We explored the role of a zinc finger transcription factor Yin Yang 1 (YY1) that is expressed in astrocytes. We found that specific deletion of YY1 from astrocytes causes severe motor deficits in mice, induces Bergmann gliosis, and results in simultaneous loss of GFAP expression in velate and fibrous cerebellar astrocytes. Single cell RNA-seq analysis showed that YY1 exerts specific effects on gene expression in subpopulations of cerebellar astrocytes. We found that although YY1 is dispensable for the initial stages of astrocyte development, it regulates subtype-specific gene expression during astrocyte maturation. Moreover, YY1 is continuously needed to maintain astrocyte identity in the adult cerebellum. Our findings suggest that YY1 plays critical roles regulating cerebellar astrocyte maturation during development and maintaining a mature phenotype of astrocytes in the adult cerebellum.
Project description:Protein post-translational modification (PTM) increases the functional diversity of the proteome and regulates numerous biological processes in eukaryotes. Two types of PTMs, O-linked-acetyl glucosamine modification (O-GlcNAc) and phosphorylation have been identified on the same amino acid, are considered as Yin-Yang modification for their antagonistic function recently. Vernalization, a prolonged cold exposure promoted flowering, is important for grain yield in temperate cereals, such as winter wheat. O-GlcNAcylation on TaGRP2 and phosphorylation on VER2 are involved in regulation of vernalization response (VRN) genes. However, less is known about how plant senses vernalization with general Yin-Yang modifications. Here we report that altering O-GlcNAc signaling by chemical inhibitors could change the vernalization response and affect flowering transition. Furthermore, we enriched O-GlcNAcylated and phosphorylated peptides from winter wheat plumules at different processing time points during vernalization by Lectin weak affinity chromatography (LWAC) and iTRAQ-TiO2, respectively. In total, about 200 O-GlcNAcylated proteins and 124 differential expressed phosphorylated proteins were identified by Mass Spectrum (MS). Based on GO enrichment, the identified O-GlcNAcylated proteins are mainly involved in response to abiotic stimulus and hormone, metabolic processing and gene expression. While dynamic phosphorylated proteins during vernalization participate in translation, transcription and metabolic processing. Of note, 31 proteins with both phosphorylation and O-GlcNAcylation modification were identified. Among them, TaGRP2 was further confirmed to participate in regulation of vernalization promoted flowering. The global modification profiles and genetic data at specific regulator suggested that the dynamic network of O-GlcNAcylation and phosphorylation on the key nodes regulate vernalization response and mediate flowering in wheat.
Project description:Protein post-translational modification (PTM) increases the functional diversity of the proteome and regulates numerous biological processes in eukaryotes. Two types of PTMs, O-linked-acetyl glucosamine modification (O-GlcNAc) and phosphorylation have been identified on the same amino acid, are considered as Yin-Yang modification for their antagonistic function recently. Vernalization, a prolonged cold exposure promoted flowering, is important for grain yield in temperate cereals, such as winter wheat. O-GlcNAcylation on TaGRP2 and phosphorylation on VER2 are involved in regulation of vernalization response (VRN) genes. However, less is known about how plant senses vernalization with general Yin-Yang modifications. Here we report that altering O-GlcNAc signaling by chemical inhibitors could change the vernalization response and affect flowering transition. Furthermore, we enriched O-GlcNAcylated and phosphorylated peptides from winter wheat plumules at different processing time points during vernalization by Lectin weak affinity chromatography (LWAC) and iTRAQ-TiO2, respectively. In total, about 200 O-GlcNAcylated proteins and 124 differential expressed phosphorylated proteins were identified by Mass Spectrum (MS). Based on GO enrichment, the identified O-GlcNAcylated proteins are mainly involved in response to abiotic stimulus and hormone, metabolic processing and gene expression. While dynamic phosphorylated proteins during vernalization participate in translation, transcription and metabolic processing. Of note, 31 proteins with both phosphorylation and O-GlcNAcylation modification were identified. Among them, TaGRP2 was further confirmed to participate in regulation of vernalization promoted flowering. The global modification profiles and genetic data at specific regulator suggested that the dynamic network of O-GlcNAcylation and phosphorylation on the key nodes regulate vernalization response and mediate flowering in wheat.